The present invention is concerned with O-substituted oxime derivatives of 3-formylrifamycin SV.
The oxime of 3-formylrifamycin SV and its O-methyl and O-morpholinoethyl derivatives are described in U.S. Pat. No. 3,342,810. These compounds although possessing a good antibacterial activity have practically no effect against bacteria which had become resistant to the other rifamycins, namely the most known and therapeutically useful 3-(4-methyl-1-piperazinyl-iminomethyl)-rifamycin SV (rifampicin).
It is well known by those who are expert in the antibiotic field that when a microorganism strain becomes resistant to a particular antibiotic drug, it is rather difficult to find another compound of the same antibiotic family which is capable to inhibit the growth of said resistant mutant. In some instances it is quite difficult to find compounds which are active against such a resistant strain even among the other different species of antibiotics.
We have surprisingly found that by substituting the hydrogen atom of the oximino group of 3-formylrifamycin SV oxime by an alkyl radical with at least 2 carbon atoms or some other suitable radical very promising compounds may be obtained which are able to exhibit at low concentrations the growth of strains resistant to the other rifamycins.
In particular, compounds of the invention display a good inhibiting effect against the rifampicin resistant Staphylococcus aureus strains. In representative experiments in vitro with the compounds of Examples 6, 8, 13, 16, 21, 23 and 25, the growth of a Staphylococcus aureus Tour strain, resistant to rifampicin, was inhibited by concentrations ranging from 1 to 5 .mu.g/ml.
This particular activity is moreover coupled with a good general effect against the other microorganisms which are usually sensitive to the rifamycins.
The invention compounds are generally very active also against the usual Gram positive and Gram negative bacteria. In particular they show a remarkable activity against Staphylococcus aureus, Streptococcus faecalis, Streptococcus hemolyticus and Diplococcus pneumoniae strains. In these cases the minimum inhibiting concentration ranges from about 0.001 to about 0.5 .mu.g/mg.
Another very important feature of the invention is the activity of certain of the compounds in inhibiting the activity of DNA polymerases.